The Transgenic Mouse and Embryonic Stem Cell Facility is a shared facility designed to generate transgenic and knockout mice for researchers at the University of Chicago. Most of these experiments are being conducted by members of the University of Chicago Cancer Research Center, and many of these experiments have direct implications not only for our understanding of cancer, but also for generating animal model systems that will be important for developing new and improved diagnostic and therapeutic tools for cancer. Five services are currently provided by the Facility: (1) preparation of transgenic mice, through the F1 generation; (2) embryo freezing; (3) clean mouse strain rederivation from either frozen embryos or embryos obtained from non-pathogen free mice; (4) transfer of embryonic stem cells to mouse blastocysts, and subsequent generation of chimeric, heterozygous and homozygous mice targeted for a particular null mutation and (5) timed mouse pregnancies. Projects carried out by the facility have been funded by a peer-reviewed federal or private grant, and the experimental protocol receives prior approval from the University Animal Care Committee. Projects include: (l) targeting growth factors and cytokines to stratified squamous epithelia, and examining the relation of these alterations to hyperproliferative disorders of the epidermis; (2) altering the expression of cell survival factors in mice and examining the molecular consequences; (3) perturbing growth control and inflammatory responses in cells of the immune system; (4) examining the roles of chromosomal breakpoint genes on tumorigenesis; (5) examining the functions of transcription factors on cell-type specific gene expression, development and differentiation, and assessing the biological consequences and relevance to cancer when they are misregulated; (6) exploring mechanisms of somatic hypermutation of genes in B-cell development; (7) understanding the mechanisms underlying processing and presentation of major histocompatibility antigens, and how these processes can go awry in genetic disorders. These studies have been central to the investigative goals of cancer researchers on campus; the contributions are of fundamental importance to our understanding of cancer.